Ginsenoside RK3 inhibits glioblastoma by modulating macrophage M2 polarization via the PPARG/CCL2 axis

Background: Glioblastoma is recognized as the most aggressive form of intracranial tumor, presenting significant challenges in treatment. Recent emphasis has been placed on the potential of traditional Chinese medicine (TCM) as an adjuvant treatment for cancer.

Methods: We employed a series of assays-including CCK8, EdU, Transwell, and neurosphere formation-to evaluate the impact of ginsenoside RK3 on the phenotype of GBM. The modulation of macrophage M2 polarization by ginsenoside RK3 was assessed through flow cytometry, immunohistochemistry, and Western blot analysis. Furthermore, we utilized sequencing analysis and network pharmacology to identify potential therapeutic targets.

Results: Our findings reveal that ginsenoside RK3 not only inhibits the phenotype of glioblastoma cells but also suppresses tumor progression in vivo while attenuating macrophage M2 polarization within the tumor immune microenvironment. Notably, ginsenoside RK3 down-regulates PPARG expression in tumor cells, leading to decreased secretion of CCL2, which subsequently diminishes macrophage M2 polarization. Additionally, we demonstrated that combining ginsenoside RK3 with temozolomide significantly enhances the inhibition of glioblastoma's malignant characteristics and progression.

Conclusions: This study innovatively highlights the dual mechanism of ginsenoside RK3 in glioblastoma treatment: it impedes tumor progression by modulating the PPARG/CCL2 pathway and enhances the efficacy of temozolomide. Our research underscores the promising role of herbal medicine in the management of glioblastoma, paving the way for novel therapeutic strategies that integrate traditional approaches with conventional treatments.